Hepatocellular Carcinoma
Conditions
Brief summary
This study will evaluate the safety, tolerability, pharmacokinetic and efficacy of fisogatinib (formerly known as BLU-554) in combination with CS1001 in patients with locally advanced or metastatic hepatocellular carcinoma (HCC)
Interventions
DRUGPhase Ib: Fisogatinib (BLU-554) 400mg in combination with Sugemalimab (CS1001) 1200mg
Phase Ib: participants received 400 mg Fisogatinib (BLU-554) once daily (QD), in combination with 1200mg fixed dose Sugemalimab (CS1001) once every 3 weeks (Q3W). Every 21 days (3 weeks) will be considered as one cycle.
DRUGPhase Ib: Fisogatinib (BLU-554) 600mg in combination with Sugemalimab (CS1001) 1200mg
Phase Ib: participants received 600 mg Fisogatinib (BLU-554) QD, in combination with 1200mg fixed dose Sugemalimab (CS1001) Q3W. Every 21 days (3 weeks) will be considered as one cycle.
DRUGPhase II: Fisogatinib (BLU-554) 600mg in combination with Sugemalimab (CS1001) 1200mg
Phase II: participants received 600 mg Fisogatinib (BLU-554) QD, in combination with 1200mg fixed dose Sugemalimab (CS1001) Q3W. Every 21 days (3 weeks) will be considered as one cycle.
Sponsors
Blueprint Medicines Corporation
CStone Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Voluntarily participate in the clinical study. Fully understand and get informed of this study and sign the Informed Consent Form (ICF). 2. ≥18 years of age on day of signing the informed consent. 3. Unresectable locally advanced or metastatic hepatocellular carcinoma as confirmed by histology or cytology. 4. Stage B or C based on Barcelona Clinic Liver Cancer (BCLC) staging system; In case of Stage B, subject must be ineligible for surgery and/or local therapy, or has progressed after surgery and/or local therapy or refuses surgery and/or local treatment. 5. For Phase Ib, subject has failed after or is unsuitable for the standard systemic therapy against HCC. For Phase II, subject has not previously received systemic therapy. 6. At least one measurable lesion as evaluable by RECIST version 1.1. 7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0-1 point. 8. A-level Child-Pugh score. 9. Expected survival≥3 months. 10. For Phase Ib and II, fresh or archived tumor tissue should be provided for analysis in the central laboratory. 11. The function of the main organs was basically normal and met the requirements of the protocol. 12. For subject with HCV infection, HCV antiviral treatment with the locally approved and available HCV antiviral therapy can be received. 13. For subjects with HBV infection, HBV DNA ≤ 2,000 IU/ml at Screening. 14. For female subjects of childbearing potential, serum pregnancy test must be negative within 7 days prior to randomization. Except for female subjects who have been recorded as surgically sterilized or who are postmenopausal, female subjects of childbearing potential or male subjects and their partners must agree to use effective contraception from the signature of the informed consent form (ICF) until at least 6 months after the last dose of study drug.
Exclusion criteria
1. tumor thrombus in the main portal vein (VP4) by imaging, involving the inferior vena cava or the heart. 2. Prior history of hepatic encephalopathy. 3. History of liver surgery and/or local treatment for HCC (intervention, ablation therapy, absolute alcohol injection, etc.) or radiotherapy, etc. within 4 weeks prior to first dose. 4. Active or documented gastrointestinal bleeding within 6 months (e.g. esophageal or gastric varices, ulcer bleeding). 5. Presence of ascites detected by physical examination or clinical symptoms caused by ascites during the screening period, or ascites that need for special treatment, such as repeated drainage, intraperitoneal drug infusion, etc. 6. Presence of meningeal metastasis or central nervous system (CNS) metastatic lesions. 7. Subject has clinically significant, uncontrolled cardiovascular disease. 8. History of definite interstitial lung disease or non-infectious pneumonia except that caused by local radiotherapy; history of active tuberculosis. 9. Any serious acute, chronic infections that require systemic antimicrobial, antifungal or antiviral therapy at screening, excluding viral hepatitis. 10. Malabsorption syndrome or inability to take the study drug orally for other reasons. 11. Had primary malignancies other than HCC within 5 years. 12. Subject has had major surgery within 4 weeks prior to first dose (procedures such as central venous cannulation, biopsy, and feeding tube placement are not considered as major surgery). 13. Previously received FGFR4 inhibitor treatment. 14. Blood transfusion, use of hematopoietic stimulating factors \[including G-CSF (granulocyte colony stimulating factor), GM-CSF (granulocyte-macrophage colony stimulating factor), EPO (erythropoietin) and TPO (thrombopoietin)\] and human albumin preparations within 14 days prior to first dose. 15. Requiring corticosteroids (dose equivalent to \> 10 mg/day of Prednisone) or other immunosuppressive drugs within 14 days prior to first dose for systemic therapy. 16. Use of traditional Chinese medicine with anti-liver cancer indication within 14 days prior to the first dose. 17. Subject has received potent CYP3A4 inhibitors and/or inducers within 2 weeks prior to first dose. 18. Concurrent HBV and HCV infection. 19. Subjects with known human immunodeficiency virus (HIV) infection. 20. Lactating women. 21. Subjects with a history of hypersensitivity or hypersensitivity to any of the components of the investigational drug. 22. Circumstances that in the opinion of the investigator would preclude participation in the study. 23. Subjects who are unwilling or unable to follow the study procedures as defined. 24. With the exception of alopecia, all toxicities from prior anticancer therapies and other therapies did not recover to ≤ Grade 1 (per CTCAE v5.0) prior to the first dose of study drug. 25. Subjects who have received prior allogeneic stem cell or solid organ transplantation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase Ib: Patients With Event(s) of Dose-limiting Toxicity | Cycle 1 (21 days) of treatment | Number of DLT (Dose-limiting toxicity) During the Administration of BLU-554 in Combination with CS1001. All toxicity or adverse events (AEs) are graded according to NCI-CTCAE 5.0. Any AE occurring during C1 (21 days) that is not clearly caused by something other than investigational drug. |
| Phase Ib: Safety and Tolerance | Safety and tolerance assessments continued for the duration of treatment. AEs and SAEs will be collected from time of signature of main informed consent, throughout the treatment period and including the follow-up period, up to approximate 22 months. | An AE was any untoward medical occurrence after clinical study subjects receive study drug. An SAE was any event that meets any the following criteria: death, life-threatening; inpatient hospitalization or prolongation, persistent or significant disability/incapacity;congenital malformation/birth defects and significant medical events. AE and SAE were graded by CTCAE version 5.0 by severity, from Grade 1 mild to Grade 5 death related AE. |
| Phase II: Objective Response Rate (ORR) Assessed by Investigator Based on RECIST Version 1.1 | Imaging (CT or MRI) assessments per RECIST v1.1 will be performed within 28 days prior to the first dose (baseline assessment), every 9 weeks during the first year of the study, and every 12 weeks thereafter. Up to 22 months. | Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1 .1) for target lesions and assessed by MRI/ CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \> =30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR. Percentage of subjects who achieve objective tumor response (CR or PR) will be summarized. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patients With Anti-CS1001 Antibody | Pre-dose of Cycle 1, 2, 4, 5, 7, 10, 13, 16 and every 8 cycles thereafter. Up to 22 months. | — |
| Overall Survival | Subject should be followed from time of registration till the time of subject death. Up to 22 months. | Overall survival is defined as the time interval between the date of the first investigational product dose to the date of death from any cause |
| Disease Control Rate by PD-L1 Protein Level | Imaging (CT or MRI) assessments by FGF19 protein and PD-L1 protein level will be performed within 28 days prior to the first dose (baseline assessment), every 9 weeks during the first year of the study, and every 12 weeks thereafter. Up to 22 months. | — |
| Objective Response Rate (ORR) by PD-L1 Protein Level | Imaging (CT or MRI) assessments by FGF19 protein and PD-L1 protein level will be performed within 28 days prior to the first dose (baseline assessment), every 9 weeks during the first year of the study, and every 12 weeks thereafter. Up to 22 months. | — |
| Progression-free Survival Assessed by Investigator | Imaging (CT or MRI) assessments per RECIST v1.1 will be performed within 28 days prior to the first dose (baseline assessment), every 9 weeks during the first year of the study, and every 12 weeks thereafter. Up to 22 months. | Progression-free Survival is defined as the time from the date of first study dose to disease progression or death (whichever occurs first). |
| Time to Progression Assessed by Investigator | Imaging (CT or MRI) assessments per RECIST v1.1 will be performed within 28 days prior to the first dose (baseline assessment), every 9 weeks during the first year of the study, and every 12 weeks thereafter. Up to 22 months. | Time to Progression is defined as the time from the date of first study dose to disease progression. Subjects without event (no disease progression) will be censored at the date of last tumor assessment. |
| Phase II: Safety and Tolerance | Safety and tolerance assessments continued for the duration of treatment. AEs and SAEs will be collected from time of signature of main informed consent, throughout the treatment period and including the follow-up period, up to approximate 22 months. | An AE was any untoward medical occurrence after clinical study subjects receive study drug. An SAE was any event that meets any the following criteria: death, life-threatening; inpatient hospitalization or prolongation, persistent or significant disability/incapacity;congenital malformation/birth defects and significant medical events. AE and SAE were graded by CTCAE version 5.0 by severity, from Grade 1 mild to Grade 5 death related AE. |
| Pharmacokinetic Parameters of Accumulation Ratio of Fisogatinib (BLU-554) | For BLU554, Cycle 1 day 1( 0, 0.5 to 24 hour post dose) and Cycle 2 day 1( 0, 0.5 to 24 hour post dose). | Pharmacokinetic(PK) parameters of accumulation ratio of Fisogatinib (BLU-554),Rac,AUC. Only participants with evaluable PK results were included in the analysis. Where data is not presented, the PK profiles were non-measurable. Results for Phase Ib and Phase II have been pooled for the same dosage. |
| Disease Control Rate Assessed by Investigator | Imaging (CT or MRI) assessments per RECIST v1.1 will be performed within 28 days prior to the first dose (baseline assessment), every 9 weeks during the first year of the study, and every 12 weeks thereafter. Up to 22 months. | Disease control rate (DCR) is defined as the proportion of participants who achieve complete response (CR), partial response (PR), and stable disease (SD) based on Response Evaluation Criteria In Solid Tumors (RECIST)v1.1. Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1 .1) for target lesions and assessed by MRI/ CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \> =30% decrease in the sum of the longest diameter of target lesions. Stable disease(SD) is defined as a tumor that does not meet the criteria for progression or for response. |
| Pharmacokinetic Parameters of Clearance at Steady State (CLss) of Fisogatinib (BLU-554) | For BLU554, Cycle 1 day 1( 0, 0.5 to 24 hour post dose) and Cycle 2 day 1( 0, 0.5 to 24 hour post dose). | Pharmacokinetic Parameters of Clearance at Steady State (Clss) of Fisogatinib (BLU-554). Only participants with evaluable PK results were included in the analysis. Where data is not presented, the PK profiles were non-measurable. Results for Phase Ib and Phase II have been pooled for the same dosage. |
| Pharmacokinetic Parameters of Maximum Serum Concentration (Cmax) of Fisogatinib (BLU-554) | For BLU554, Cycle 1 day 1( 0, 0.5 to 24 hour post dose) and Cycle 2 day 1( 0, 0.5 to 24 hour post dose). | PK Parameters of Cmax of Fisogatinib (BLU-554). Only participants with evaluable PK results were included in the analysis. Where data is not presented, the PK profiles were non-measurable. Results for Phase Ib and Phase II have been pooled for the same dosage. |
| Pharmacokinetic Parameters of Time to Maximum Serum Concentration (Tmax) of Fisogatinib (BLU-554) | For BLU554, Cycle 1 day 1( 0, 0.5 to 24 hour post dose) and Cycle 2 day 1( 0, 0.5 to 24 hour post dose). | PK Parameters of Tmax of Fisogatinib (BLU-554). Only participants with evaluable PK results were included in the analysis. Where data is not presented, the PK profiles were non-measurable. Results for Phase Ib and Phase II have been pooled for the same dosage. |
| Pharmacokinetic Parameters of Accumulation Ratio of Sugemalimab (CS1001) | For CS1001: Cycle 1 day 1(0, 0.5 to 504 hour post dose) and Cycle 4 day 1 (0, 0.5 to 504 hour post dose). | PK Parameters of Rac, AUC of Sugemalimab (CS1001). Only participants with evaluable PK results were included in the analysis. Where data is not presented, the PK profiles were non-measurable. Results for Phase Ib and Phase II have been pooled for the same dosage. |
| Pharmacokinetic Parameters of Area Under the Serum Concentration-time Curve (AUC ) of Sugemalimab (CS1001) | For CS1001: Cycle 1 day 1(0, 0.5 to 504 hour post dose) and Cycle 4 day 1 (0, 0.5 to 504 hour post dose). | PK Parameters of (AUC 0-τ,ss ) of Sugemalimab (CS1001). Only participants with evaluable PK results were included in the analysis. Where data is not presented, the PK profiles were non-measurable. Results for Phase Ib and Phase II have been pooled for the same dosage. |
| Pharmacokinetic Parameters of Clearance at Steady State (CLss) of Sugemalimab (CS1001) | For CS1001: Cycle 1 day 1(0, 0.5 to 504 hour post dose) and Cycle 4 day 1 (0, 0.5 to 504 hour post dose). | PK Parameters of CLss of Sugemalimab (CS1001). Only participants with evaluable PK results were included in the analysis. Where data is not presented, the PK profiles were non-measurable. Results for Phase Ib and Phase II have been pooled for the same dosage. |
| Pharmacokinetic Parameters of Maximum Serum Concentration (Cmax) of Sugemalimab (CS1001) | For CS1001: Cycle 1 day 1(0, 0.5 to 504 hour post dose) and Cycle 4 day 1 (0, 0.5 to 504 hour post dose). | PK Parameters of Cmax of Sugemalimab (CS1001). Only participants with evaluable PK results were included in the analysis. Where data is not presented, the PK profiles were non-measurable. Results for Phase Ib and Phase II have been pooled for the same dosage. |
| Pharmacokinetic Parameters of Time to Maximum Serum Concentration (Tmax) of Sugemalimab (CS1001) | For CS1001: Cycle 1 day 1(0, 0.5 to 504 hour post dose) and Cycle 4 day 1 (0, 0.5 to 504 hour post dose). | PK Parameters of Tmax of Sugemalimab (CS1001). Only participants with evaluable PK results were included in the analysis. Where data is not presented, the PK profiles were non-measurable. Results for Phase Ib and Phase II have been pooled for the same dosage. |
| Pharmacokinetic Parameters of Area Under the Serum Concentration-time Curve (AUC) of Fisogatinib (BLU-554) | For BLU554, Cycle 1 day 1( 0, 0.5 to 24 hour post dose) and Cycle 2 day 1( 0, 0.5 to 24 hour post dose). | Pharmacokinetic parameters of area under the serum concentration-time curve (AUC0-τ,ss, Time from 0 to 24h) of Fisogatinib (BLU-554). Only participants with evaluable PK results were included in the analysis. Where data is not presented, the PK profiles were non-measurable. Results for Phase Ib and Phase II have been pooled for the same dosage. |
| Duration of Response Assessed by Investigator | Imaging (CT or MRI) assessments per RECIST v1.1 will be performed within 28 days prior to the first dose (baseline assessment), every 9 weeks during the first year of the study, and every 12 weeks thereafter. Up to 22 months. | Duration of response for responders (CR or PR) is defined as the time interval between the date of the earliest qualifying response and the date of PD or death for any cause (whichever occurs earlier). For subjects who are alive without progression following the qualifying response, duration of response will be censored on the date of last evaluable tumor assessment or last follow-up for progression of disease. |
| Phase Ib: Objective Response Rate (ORR) Assessed by Investigator Based on RECIST Version 1.1 | Imaging (CT or MRI) assessments per RECIST v1.1 will be performed within 28 days prior to the first dose (baseline assessment), every 9 weeks during the first year of the study, and every 12 weeks thereafter. Up to 22 months. | Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1 .1) for target lesions and assessed by MRI/ CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \> =30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR. Percentage of subjects who achieve objective tumor response (CR or PR) will be summarized. |
Countries
China
Participant flow
Recruitment details
Participants were screened across 19 centers and enrolled across 11 centers in China. The study consists of 2 parts, including Phase Ib dose escalation and Phase II dose expansion. A total of 26 participants were enrolled in the study and all received ≥ 1 dose of study drug.
Participants by arm
| Arm | Count |
|---|---|
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg Phase Ib: participants received 400 mg Fisogatinib (BLU-554) once daily (QD), in combination with 1200mg fixed dose Sugemalimab (CS1001) once every 3 weeks (Q3W). Every 21 days (3 weeks) will be considered as one cycle. | 4 |
| Phase Ib: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg Phase Ib: participants received 600 mg Fisogatinib (BLU-554) QD, in combination with 1200mg fixed dose Sugemalimab (CS1001) Q3W. Every 21 days (3 weeks) will be considered as one cycle. | 7 |
| Phase II: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg Phase II: participants received 600 mg Fisogatinib (BLU-554) QD, in combination with 1200mg fixed dose Sugemalimab (CS1001) Q3W. Every 21 days (3 weeks) will be considered as one cycle. | 15 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Part Ib/II End of Study | Death | 2 | 3 | 3 |
| Part Ib/II End of Study | Lost to Follow-up | 0 | 1 | 0 |
| Part Ib/II End of Study | Ongoing treatment | 0 | 0 | 2 |
| Part Ib/II End of Study | Study ended by sponsor | 1 | 3 | 8 |
| Part Ib/II End of Study | Withdrawal by Subject | 1 | 0 | 2 |
| Part Ib/II End Of Treatment-BLU554 | Adverse Event | 0 | 2 | 1 |
| Part Ib/II End Of Treatment-BLU554 | Death | 0 | 0 | 1 |
| Part Ib/II End Of Treatment-BLU554 | Ongoing treatment | 0 | 0 | 2 |
| Part Ib/II End Of Treatment-BLU554 | Other | 0 | 0 | 2 |
| Part Ib/II End Of Treatment-BLU554 | Physician Decision | 1 | 0 | 0 |
| Part Ib/II End Of Treatment-BLU554 | Radiographic disease progression | 3 | 4 | 9 |
| Part Ib/II End Of Treatment-BLU554 | Symptomatic deterioration without radiographic evidence | 0 | 1 | 0 |
| Part Ib/II End Of Treatment-CS1001 | Adverse Event | 1 | 0 | 2 |
| Part Ib/II End Of Treatment-CS1001 | Death | 0 | 0 | 1 |
| Part Ib/II End Of Treatment-CS1001 | Ongoing treatment | 0 | 0 | 2 |
| Part Ib/II End Of Treatment-CS1001 | Other | 0 | 0 | 1 |
| Part Ib/II End Of Treatment-CS1001 | Radiographic disease progression | 3 | 6 | 9 |
| Part Ib/II End Of Treatment-CS1001 | Symptomatic deterioration without radiographic evidence | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Phase Ib: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Phase II: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Total | Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 2 Participants | 3 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 13 Participants | 23 Participants | 4 Participants |
| Age, Continuous | 48.4 Years STANDARD_DEVIATION 11.82 | 51.6 Years STANDARD_DEVIATION 12.37 | 49.5 Years STANDARD_DEVIATION 11.43 | 43.5 Years STANDARD_DEVIATION 4.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants | 15 Participants | 26 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment China | 7 Participants | 15 Participants | 26 Participants | 4 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 4 Participants | 1 Participants |
| Sex: Female, Male Male | 5 Participants | 14 Participants | 22 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 4 | 3 / 7 | 3 / 15 |
| other Total, other adverse events | 4 / 4 | 7 / 7 | 15 / 15 |
| serious Total, serious adverse events | 1 / 4 | 2 / 7 | 5 / 15 |
Outcome results
Primary
Phase Ib: Patients With Event(s) of Dose-limiting Toxicity
Number of DLT (Dose-limiting toxicity) During the Administration of BLU-554 in Combination with CS1001. All toxicity or adverse events (AEs) are graded according to NCI-CTCAE 5.0. Any AE occurring during C1 (21 days) that is not clearly caused by something other than investigational drug.
Time frame: Cycle 1 (21 days) of treatment
Population: Fisogatinib (BLU-554) 600mg arm, 7 subjects were enrolled, of whom 6 completed DLT evaluation and 1 was unevaluable
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Phase Ib: Patients With Event(s) of Dose-limiting Toxicity | 0 Participants |
| Phase Ib: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Phase Ib: Patients With Event(s) of Dose-limiting Toxicity | 0 Participants |
Primary
Phase Ib: Safety and Tolerance
An AE was any untoward medical occurrence after clinical study subjects receive study drug. An SAE was any event that meets any the following criteria: death, life-threatening; inpatient hospitalization or prolongation, persistent or significant disability/incapacity;congenital malformation/birth defects and significant medical events. AE and SAE were graded by CTCAE version 5.0 by severity, from Grade 1 mild to Grade 5 death related AE.
Time frame: Safety and tolerance assessments continued for the duration of treatment. AEs and SAEs will be collected from time of signature of main informed consent, throughout the treatment period and including the follow-up period, up to approximate 22 months.
Population: Baseline Analysis Population consists of all participants receiving at least one dose of investigational product
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Phase Ib: Safety and Tolerance | Infusion-related reaction TEAE | 0 Participants |
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Phase Ib: Safety and Tolerance | Treatment-Emergent Adverse Event（TEAE） | 4 Participants |
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Phase Ib: Safety and Tolerance | TEAE Leading to CS1001 rate of infusion modification | 0 Participants |
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Phase Ib: Safety and Tolerance | Serious TEAE | 1 Participants |
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Phase Ib: Safety and Tolerance | TEAE Leading to CS1001 dose interruption | 0 Participants |
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Phase Ib: Safety and Tolerance | Grade 3-5 TEAE | 2 Participants |
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Phase Ib: Safety and Tolerance | TEAE Leading to CS1001 permanently discontinuation | 1 Participants |
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Phase Ib: Safety and Tolerance | TEAE Leading to BLU-554 dose reduction | 0 Participants |
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Phase Ib: Safety and Tolerance | Serious TEAE at least one related to CS1001 or BLU-554 | 0 Participants |
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Phase Ib: Safety and Tolerance | TEAE Leading to BLU-554 dose interruption | 1 Participants |
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Phase Ib: Safety and Tolerance | TEAE at least one related to CS1001 or BLU-554 | 4 Participants |
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Phase Ib: Safety and Tolerance | TEAE Leading to BLU-554 permanently discontinuation | 0 Participants |
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Phase Ib: Safety and Tolerance | Immune-related TEAE | 2 Participants |
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Phase Ib: Safety and Tolerance | TEAE Leading to death | 0 Participants |
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Phase Ib: Safety and Tolerance | Grade 3-5 TEAE at least one related to CS1001 or BLU-554 | 1 Participants |
| Phase Ib: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Phase Ib: Safety and Tolerance | TEAE Leading to death | 1 Participants |
| Phase Ib: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Phase Ib: Safety and Tolerance | Treatment-Emergent Adverse Event（TEAE） | 7 Participants |
| Phase Ib: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Phase Ib: Safety and Tolerance | TEAE at least one related to CS1001 or BLU-554 | 6 Participants |
| Phase Ib: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Phase Ib: Safety and Tolerance | Grade 3-5 TEAE | 6 Participants |
| Phase Ib: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Phase Ib: Safety and Tolerance | Grade 3-5 TEAE at least one related to CS1001 or BLU-554 | 4 Participants |
| Phase Ib: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Phase Ib: Safety and Tolerance | Serious TEAE | 2 Participants |
| Phase Ib: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Phase Ib: Safety and Tolerance | Serious TEAE at least one related to CS1001 or BLU-554 | 1 Participants |
| Phase Ib: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Phase Ib: Safety and Tolerance | Immune-related TEAE | 2 Participants |
| Phase Ib: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Phase Ib: Safety and Tolerance | Infusion-related reaction TEAE | 0 Participants |
| Phase Ib: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Phase Ib: Safety and Tolerance | TEAE Leading to CS1001 rate of infusion modification | 0 Participants |
| Phase Ib: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Phase Ib: Safety and Tolerance | TEAE Leading to CS1001 dose interruption | 2 Participants |
| Phase Ib: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Phase Ib: Safety and Tolerance | TEAE Leading to BLU-554 dose reduction | 2 Participants |
| Phase Ib: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Phase Ib: Safety and Tolerance | TEAE Leading to BLU-554 dose interruption | 1 Participants |
| Phase Ib: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Phase Ib: Safety and Tolerance | TEAE Leading to BLU-554 permanently discontinuation | 2 Participants |
| Phase Ib: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Phase Ib: Safety and Tolerance | TEAE Leading to CS1001 permanently discontinuation | 0 Participants |
Primary
Phase II: Objective Response Rate (ORR) Assessed by Investigator Based on RECIST Version 1.1
Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1 .1) for target lesions and assessed by MRI/ CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \> =30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR. Percentage of subjects who achieve objective tumor response (CR or PR) will be summarized.
Time frame: Imaging (CT or MRI) assessments per RECIST v1.1 will be performed within 28 days prior to the first dose (baseline assessment), every 9 weeks during the first year of the study, and every 12 weeks thereafter. Up to 22 months.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Phase II: Objective Response Rate (ORR) Assessed by Investigator Based on RECIST Version 1.1 | Responder | 3 Participants |
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Phase II: Objective Response Rate (ORR) Assessed by Investigator Based on RECIST Version 1.1 | Non-Responder | 12 Participants |
Secondary
Disease Control Rate Assessed by Investigator
Disease control rate (DCR) is defined as the proportion of participants who achieve complete response (CR), partial response (PR), and stable disease (SD) based on Response Evaluation Criteria In Solid Tumors (RECIST)v1.1. Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1 .1) for target lesions and assessed by MRI/ CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \> =30% decrease in the sum of the longest diameter of target lesions. Stable disease(SD) is defined as a tumor that does not meet the criteria for progression or for response.
Time frame: Imaging (CT or MRI) assessments per RECIST v1.1 will be performed within 28 days prior to the first dose (baseline assessment), every 9 weeks during the first year of the study, and every 12 weeks thereafter. Up to 22 months.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Disease Control Rate Assessed by Investigator | 1 Participants |
| Phase Ib: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Disease Control Rate Assessed by Investigator | 3 Participants |
| Phase II: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Disease Control Rate Assessed by Investigator | 9 Participants |
Secondary
Disease Control Rate by PD-L1 Protein Level
Time frame: Imaging (CT or MRI) assessments by FGF19 protein and PD-L1 protein level will be performed within 28 days prior to the first dose (baseline assessment), every 9 weeks during the first year of the study, and every 12 weeks thereafter. Up to 22 months.
Population: Efficacy analysis dataset with dichotomous PD-L1 parameters at baseline.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Disease Control Rate by PD-L1 Protein Level | 2 Participants |
| Phase Ib: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Disease Control Rate by PD-L1 Protein Level | 7 Participants |
| Phase II: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Disease Control Rate by PD-L1 Protein Level | 8 Participants |
| Phase II: BLU-554 600mg in Combination With CS1001 1200mg With TC Percentage >=1 Percentage | Disease Control Rate by PD-L1 Protein Level | 1 Participants |
Secondary
Duration of Response Assessed by Investigator
Duration of response for responders (CR or PR) is defined as the time interval between the date of the earliest qualifying response and the date of PD or death for any cause (whichever occurs earlier). For subjects who are alive without progression following the qualifying response, duration of response will be censored on the date of last evaluable tumor assessment or last follow-up for progression of disease.
Time frame: Imaging (CT or MRI) assessments per RECIST v1.1 will be performed within 28 days prior to the first dose (baseline assessment), every 9 weeks during the first year of the study, and every 12 weeks thereafter. Up to 22 months.
Population: Only include participants with confirmed response (CR or PR).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase Ib: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Duration of Response Assessed by Investigator | 4.34 Months |
| Phase II: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Duration of Response Assessed by Investigator | NA Months |
Secondary
Objective Response Rate (ORR) by PD-L1 Protein Level
Time frame: Imaging (CT or MRI) assessments by FGF19 protein and PD-L1 protein level will be performed within 28 days prior to the first dose (baseline assessment), every 9 weeks during the first year of the study, and every 12 weeks thereafter. Up to 22 months.
Population: Efficacy analysis dataset with dichotomous PD-L1 parameters at baseline.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Objective Response Rate (ORR) by PD-L1 Protein Level | 1 Participants |
| Phase Ib: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Objective Response Rate (ORR) by PD-L1 Protein Level | 2 Participants |
| Phase II: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Objective Response Rate (ORR) by PD-L1 Protein Level | 2 Participants |
| Phase II: BLU-554 600mg in Combination With CS1001 1200mg With TC Percentage >=1 Percentage | Objective Response Rate (ORR) by PD-L1 Protein Level | 1 Participants |
Secondary
Overall Survival
Overall survival is defined as the time interval between the date of the first investigational product dose to the date of death from any cause
Time frame: Subject should be followed from time of registration till the time of subject death. Up to 22 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Overall Survival | 16.2 Months |
| Phase Ib: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Overall Survival | NA Months |
| Phase II: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Overall Survival | NA Months |
Secondary
Patients With Anti-CS1001 Antibody
Time frame: Pre-dose of Cycle 1, 2, 4, 5, 7, 10, 13, 16 and every 8 cycles thereafter. Up to 22 months.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Patients With Anti-CS1001 Antibody | 0 Participants |
| Phase Ib: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Patients With Anti-CS1001 Antibody | 0 Participants |
| Phase II: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Patients With Anti-CS1001 Antibody | 0 Participants |
Secondary
Pharmacokinetic Parameters of Accumulation Ratio of Fisogatinib (BLU-554)
Pharmacokinetic(PK) parameters of accumulation ratio of Fisogatinib (BLU-554),Rac,AUC. Only participants with evaluable PK results were included in the analysis. Where data is not presented, the PK profiles were non-measurable. Results for Phase Ib and Phase II have been pooled for the same dosage.
Time frame: For BLU554, Cycle 1 day 1( 0, 0.5 to 24 hour post dose) and Cycle 2 day 1( 0, 0.5 to 24 hour post dose).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Pharmacokinetic Parameters of Accumulation Ratio of Fisogatinib (BLU-554) | 1.22 ratio | Geometric Coefficient of Variation 36.41 |
| Phase Ib: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Pharmacokinetic Parameters of Accumulation Ratio of Fisogatinib (BLU-554) | 1.35 ratio | Geometric Coefficient of Variation 42 |
Secondary
Pharmacokinetic Parameters of Accumulation Ratio of Sugemalimab (CS1001)
PK Parameters of Rac, AUC of Sugemalimab (CS1001). Only participants with evaluable PK results were included in the analysis. Where data is not presented, the PK profiles were non-measurable. Results for Phase Ib and Phase II have been pooled for the same dosage.
Time frame: For CS1001: Cycle 1 day 1(0, 0.5 to 504 hour post dose) and Cycle 4 day 1 (0, 0.5 to 504 hour post dose).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Pharmacokinetic Parameters of Accumulation Ratio of Sugemalimab (CS1001) | 1.1 ratio | Geometric Coefficient of Variation 67.01 |
| Phase Ib: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Pharmacokinetic Parameters of Accumulation Ratio of Sugemalimab (CS1001) | 2.44 ratio | Geometric Coefficient of Variation 5.85 |
Secondary
Pharmacokinetic Parameters of Area Under the Serum Concentration-time Curve (AUC) of Fisogatinib (BLU-554)
Pharmacokinetic parameters of area under the serum concentration-time curve (AUC0-τ,ss, Time from 0 to 24h) of Fisogatinib (BLU-554). Only participants with evaluable PK results were included in the analysis. Where data is not presented, the PK profiles were non-measurable. Results for Phase Ib and Phase II have been pooled for the same dosage.
Time frame: For BLU554, Cycle 1 day 1( 0, 0.5 to 24 hour post dose) and Cycle 2 day 1( 0, 0.5 to 24 hour post dose).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Pharmacokinetic Parameters of Area Under the Serum Concentration-time Curve (AUC) of Fisogatinib (BLU-554) | 55.3 h*μg/mL | Geometric Coefficient of Variation 65.43 |
| Phase Ib: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Pharmacokinetic Parameters of Area Under the Serum Concentration-time Curve (AUC) of Fisogatinib (BLU-554) | 73.8 h*μg/mL | Geometric Coefficient of Variation 29.96 |
Secondary
Pharmacokinetic Parameters of Area Under the Serum Concentration-time Curve (AUC ) of Sugemalimab (CS1001)
PK Parameters of (AUC 0-τ,ss ) of Sugemalimab (CS1001). Only participants with evaluable PK results were included in the analysis. Where data is not presented, the PK profiles were non-measurable. Results for Phase Ib and Phase II have been pooled for the same dosage.
Time frame: For CS1001: Cycle 1 day 1(0, 0.5 to 504 hour post dose) and Cycle 4 day 1 (0, 0.5 to 504 hour post dose).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Pharmacokinetic Parameters of Area Under the Serum Concentration-time Curve (AUC ) of Sugemalimab (CS1001) | 148000 h*μg/mL | — |
| Phase Ib: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Pharmacokinetic Parameters of Area Under the Serum Concentration-time Curve (AUC ) of Sugemalimab (CS1001) | 136000 h*μg/mL | Geometric Coefficient of Variation 34.14 |
Secondary
Pharmacokinetic Parameters of Clearance at Steady State (CLss) of Fisogatinib (BLU-554)
Pharmacokinetic Parameters of Clearance at Steady State (Clss) of Fisogatinib (BLU-554). Only participants with evaluable PK results were included in the analysis. Where data is not presented, the PK profiles were non-measurable. Results for Phase Ib and Phase II have been pooled for the same dosage.
Time frame: For BLU554, Cycle 1 day 1( 0, 0.5 to 24 hour post dose) and Cycle 2 day 1( 0, 0.5 to 24 hour post dose).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Pharmacokinetic Parameters of Clearance at Steady State (CLss) of Fisogatinib (BLU-554) | 7.24 L/h | Geometric Coefficient of Variation 65.43 |
| Phase Ib: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Pharmacokinetic Parameters of Clearance at Steady State (CLss) of Fisogatinib (BLU-554) | 8.13 L/h | Geometric Coefficient of Variation 29.96 |
Secondary
Pharmacokinetic Parameters of Clearance at Steady State (CLss) of Sugemalimab (CS1001)
PK Parameters of CLss of Sugemalimab (CS1001). Only participants with evaluable PK results were included in the analysis. Where data is not presented, the PK profiles were non-measurable. Results for Phase Ib and Phase II have been pooled for the same dosage.
Time frame: For CS1001: Cycle 1 day 1(0, 0.5 to 504 hour post dose) and Cycle 4 day 1 (0, 0.5 to 504 hour post dose).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Pharmacokinetic Parameters of Clearance at Steady State (CLss) of Sugemalimab (CS1001) | 0.00808 L/h | — |
| Phase Ib: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Pharmacokinetic Parameters of Clearance at Steady State (CLss) of Sugemalimab (CS1001) | 0.00821 L/h | Geometric Coefficient of Variation 23.74 |
Secondary
Pharmacokinetic Parameters of Maximum Serum Concentration (Cmax) of Fisogatinib (BLU-554)
PK Parameters of Cmax of Fisogatinib (BLU-554). Only participants with evaluable PK results were included in the analysis. Where data is not presented, the PK profiles were non-measurable. Results for Phase Ib and Phase II have been pooled for the same dosage.
Time frame: For BLU554, Cycle 1 day 1( 0, 0.5 to 24 hour post dose) and Cycle 2 day 1( 0, 0.5 to 24 hour post dose).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Pharmacokinetic Parameters of Maximum Serum Concentration (Cmax) of Fisogatinib (BLU-554) | 7.26 μg/mL | Geometric Coefficient of Variation 50.01 |
| Phase Ib: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Pharmacokinetic Parameters of Maximum Serum Concentration (Cmax) of Fisogatinib (BLU-554) | 8.14 μg/mL | Geometric Coefficient of Variation 27.52 |
Secondary
Pharmacokinetic Parameters of Maximum Serum Concentration (Cmax) of Sugemalimab (CS1001)
PK Parameters of Cmax of Sugemalimab (CS1001). Only participants with evaluable PK results were included in the analysis. Where data is not presented, the PK profiles were non-measurable. Results for Phase Ib and Phase II have been pooled for the same dosage.
Time frame: For CS1001: Cycle 1 day 1(0, 0.5 to 504 hour post dose) and Cycle 4 day 1 (0, 0.5 to 504 hour post dose).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Pharmacokinetic Parameters of Maximum Serum Concentration (Cmax) of Sugemalimab (CS1001) | 513 μg/mL | Geometric Coefficient of Variation 11.08 |
| Phase Ib: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Pharmacokinetic Parameters of Maximum Serum Concentration (Cmax) of Sugemalimab (CS1001) | 463 μg/mL | Geometric Coefficient of Variation 26.16 |
Secondary
Pharmacokinetic Parameters of Time to Maximum Serum Concentration (Tmax) of Fisogatinib (BLU-554)
PK Parameters of Tmax of Fisogatinib (BLU-554). Only participants with evaluable PK results were included in the analysis. Where data is not presented, the PK profiles were non-measurable. Results for Phase Ib and Phase II have been pooled for the same dosage.
Time frame: For BLU554, Cycle 1 day 1( 0, 0.5 to 24 hour post dose) and Cycle 2 day 1( 0, 0.5 to 24 hour post dose).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Pharmacokinetic Parameters of Time to Maximum Serum Concentration (Tmax) of Fisogatinib (BLU-554) | 1.53 hour |
| Phase Ib: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Pharmacokinetic Parameters of Time to Maximum Serum Concentration (Tmax) of Fisogatinib (BLU-554) | 2.05 hour |
Secondary
Pharmacokinetic Parameters of Time to Maximum Serum Concentration (Tmax) of Sugemalimab (CS1001)
PK Parameters of Tmax of Sugemalimab (CS1001). Only participants with evaluable PK results were included in the analysis. Where data is not presented, the PK profiles were non-measurable. Results for Phase Ib and Phase II have been pooled for the same dosage.
Time frame: For CS1001: Cycle 1 day 1(0, 0.5 to 504 hour post dose) and Cycle 4 day 1 (0, 0.5 to 504 hour post dose).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Pharmacokinetic Parameters of Time to Maximum Serum Concentration (Tmax) of Sugemalimab (CS1001) | 2.02 hour |
| Phase Ib: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Pharmacokinetic Parameters of Time to Maximum Serum Concentration (Tmax) of Sugemalimab (CS1001) | 2.12 hour |
Secondary
Phase Ib: Objective Response Rate (ORR) Assessed by Investigator Based on RECIST Version 1.1
Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1 .1) for target lesions and assessed by MRI/ CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \> =30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR. Percentage of subjects who achieve objective tumor response (CR or PR) will be summarized.
Time frame: Imaging (CT or MRI) assessments per RECIST v1.1 will be performed within 28 days prior to the first dose (baseline assessment), every 9 weeks during the first year of the study, and every 12 weeks thereafter. Up to 22 months.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Phase Ib: Objective Response Rate (ORR) Assessed by Investigator Based on RECIST Version 1.1 | Responder | 0 Participants |
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Phase Ib: Objective Response Rate (ORR) Assessed by Investigator Based on RECIST Version 1.1 | Non-Responder | 4 Participants |
| Phase Ib: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Phase Ib: Objective Response Rate (ORR) Assessed by Investigator Based on RECIST Version 1.1 | Responder | 1 Participants |
| Phase Ib: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Phase Ib: Objective Response Rate (ORR) Assessed by Investigator Based on RECIST Version 1.1 | Non-Responder | 6 Participants |
Secondary
Phase II: Safety and Tolerance
An AE was any untoward medical occurrence after clinical study subjects receive study drug. An SAE was any event that meets any the following criteria: death, life-threatening; inpatient hospitalization or prolongation, persistent or significant disability/incapacity;congenital malformation/birth defects and significant medical events. AE and SAE were graded by CTCAE version 5.0 by severity, from Grade 1 mild to Grade 5 death related AE.
Time frame: Safety and tolerance assessments continued for the duration of treatment. AEs and SAEs will be collected from time of signature of main informed consent, throughout the treatment period and including the follow-up period, up to approximate 22 months.
Population: Baseline Analysis Population consists of all participants receiving at least one dose of investigational product
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Phase II: Safety and Tolerance | Treatment-Emergent Adverse Event（TEAE） | 15 Participants |
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Phase II: Safety and Tolerance | TEAE at least one related to CS1001 or BLU-554 | 15 Participants |
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Phase II: Safety and Tolerance | Grade 3-5 TEAE | 7 Participants |
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Phase II: Safety and Tolerance | Grade 3-5 TEAE at least one related to CS1001 or BLU-554 | 6 Participants |
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Phase II: Safety and Tolerance | Serious TEAE | 5 Participants |
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Phase II: Safety and Tolerance | Serious TEAE at least one related to CS1001 or BLU-554 | 3 Participants |
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Phase II: Safety and Tolerance | Immune-related TEAE | 4 Participants |
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Phase II: Safety and Tolerance | Infusion-related reaction TEAE | 1 Participants |
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Phase II: Safety and Tolerance | TEAE Leading to CS1001 rate of infusion modification | 0 Participants |
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Phase II: Safety and Tolerance | TEAE Leading to CS1001 dose interruption | 6 Participants |
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Phase II: Safety and Tolerance | TEAE Leading to CS1001 permanently discontinuation | 2 Participants |
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Phase II: Safety and Tolerance | TEAE Leading to BLU-554 dose reduction | 8 Participants |
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Phase II: Safety and Tolerance | TEAE Leading to BLU-554 dose interruption | 4 Participants |
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Phase II: Safety and Tolerance | TEAE Leading to BLU-554 permanently discontinuation | 1 Participants |
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Phase II: Safety and Tolerance | TEAE Leading to death | 1 Participants |
Secondary
Progression-free Survival Assessed by Investigator
Progression-free Survival is defined as the time from the date of first study dose to disease progression or death (whichever occurs first).
Time frame: Imaging (CT or MRI) assessments per RECIST v1.1 will be performed within 28 days prior to the first dose (baseline assessment), every 9 weeks during the first year of the study, and every 12 weeks thereafter. Up to 22 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Progression-free Survival Assessed by Investigator | 2.3 Months |
| Phase Ib: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Progression-free Survival Assessed by Investigator | 2.1 Months |
| Phase II: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Progression-free Survival Assessed by Investigator | 4.1 Months |
Secondary
Time to Progression Assessed by Investigator
Time to Progression is defined as the time from the date of first study dose to disease progression. Subjects without event (no disease progression) will be censored at the date of last tumor assessment.
Time frame: Imaging (CT or MRI) assessments per RECIST v1.1 will be performed within 28 days prior to the first dose (baseline assessment), every 9 weeks during the first year of the study, and every 12 weeks thereafter. Up to 22 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase Ib: Fisogatinib (BLU-554) 400mg in Combination With Sugemalimab (CS1001) 1200mg | Time to Progression Assessed by Investigator | 2.3 Months |
| Phase Ib: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Time to Progression Assessed by Investigator | 3.1 Months |
| Phase II: Fisogatinib (BLU-554) 600mg in Combination With Sugemalimab (CS1001) 1200mg | Time to Progression Assessed by Investigator | 4.2 Months |